Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection

Selvi Celik; Julia Sadrian; Mario Grossi; Tomasz Czuba; Jakob Lundgren; Göran Rådegran; Thomas Laurell; J Gustav Smith; Olof Gidlöf

doi:10.1016/j.jacbts.2022.09.014

Extracellular Vesicle-Associated TWEAK Contributes to Vascular Inflammation and Remodeling During Acute Cellular Rejection

JACC Basic Transl Sci. 2023 Jan 11;8(5):439-456. doi: 10.1016/j.jacbts.2022.09.014. eCollection 2023 May.

Authors

Selvi Celik^{1

2}, Julia Sadrian¹, Mario Grossi¹, Tomasz Czuba^{1

2

3

4}, Jakob Lundgren¹, Göran Rådegran¹, Thomas Laurell⁵, J Gustav Smith^{1

2

3

4}, Olof Gidlöf^{1

2

3

4}

Affiliations

¹ Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
² Wallenberg Center for Molecular Medicine and Lund University Diabetes Center, Lund University, Lund, Sweden.
³ The Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden.
⁴ Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁵ Department of Biomedical Engineering, Lund University, Lund, Sweden.

Abstract

Acute cellular rejection (ACR) is a leading cause of graft loss and death after heart transplantation despite effective immunosuppressive therapies. The identification of factors that impair graft vascular barrier function or promote immune cell recruitment during ACR could provide new therapeutic opportunities for the treatment of patients who receive transplants. In 2 ACR cohorts, we found the extracellular vesicle-associated cytokine TWEAK to be elevated during ACR. Vesicular TWEAK promoted expression of proinflammatory genes and the release of chemoattractant cytokines from human cardiac endothelial cells. We conclude that vesicular TWEAK is a novel target with potential therapeutic implications in ACR.

Keywords: TWEAK; acute cellular rejection; chronic rejection; extracellular vesicle.